Migraine-mimicking headache and sickle cell disease: a transcranial Doppler study

Headache occurs in sickle cell disease (SCD), but its characteristics and frequency have not previously been studied. Our aim was to study patterns of headache in adults with SCD and to correlate its presence with blood flow velocities measured by transcranial Doppler (TCD) and with brain magnetic resonance imaging (MRI) abnormalities. We studied 56 adults with SCD. Twenty-eight patients (50%) had severe and frequent headaches. In 20 patients (35.7%) the headache met the International Headache Society criteria for migraine without aura. Patients with frequent and severe headache presented TCD velocities significantly higher than those without headache, or with milder headache. No correlation was found between headache and abnormalities in brain MRI. A migraine-mimicking headache occurs in SCD but we should not understand it as a primary headache because the blood flow abnormalities secondary to SCD detected by TCD seem to play an important role in these patients.     

Fear of movement (kinesiophobia), pain, and psychopathology in patients with sickle cell disease

OBJECTIVES: Fear of movement (ie, kinesiophobia) has emerged as a significant predictor of pain-related outcomes including disability and psychologic distress across various types of pain (eg, back pain, headache, fibromyalgia, complex regional pain syndrome). However, no research has examined the prevalence of kinesiophobia in adults with sickle cell disease (SCD). The purpose of this study was to assess the degree of kinesiophobia reported by African American men and women with SCD and to determine whether kinesiophobia is related to pain and psychologic distress in this population. METHODS: Sixty-seven men and women with SCD recruited from a comprehensive sickle cell treatment program in a large academic medical center completed questionnaires that assess fear of movement, pain and pain interference, and psychologic distress. RESULTS: Participants reported levels of kinesiophobia (M=30.48, SD=7.55) that were comparable to those obtained for patients with low back pain and fibromyalgia. Although pain levels did not differ by sex, men reported greater kinesiophobia than women (P=0.02). As hypothesized, higher levels of kinesiophobia were associated with greater psychologic distress, particularly Phobic Anxiety (r=0.35), Psychoticism (r=0.29), Somatization (r=0.45), Anxiety (r=0.35), Obsessive-compulsive (r=0.34), Interpersonal Sensitivity (r=0.25), Depression (r=0.29), and all 3 summary indices of the SCL-90-R (all Ps<0.05). DISCUSSION: Although and historically, pain associated with SCD has not been considered in the context of fear of movement, findings suggest that both kinesiophobia and sex are relevant constructs for consideration in understanding pain-related outcomes in SCD. Though our results require replication, this study suggests that greater kinesiophobia is associated with greater pain and psychologic distress.     

Integrative approaches to treating pain in sickle cell disease: Pre-clinical and clinical evidence

Sickle cell disease (SCD) is a genetic disorder characterized by hemolysis, end-organ damage, inflammation, and pain. Recurrent and unpredictable episodes of acute pain due to vaso-occlusive crises are a unique feature of SCD. Many patients also develop lifelong chronic pain. Opioids are the primary method of pain treatment in SCD; however, continued use is associated with several adverse effects. Integrative approaches to treating pain in SCD are increasingly being explored to prevent the side effects associated with opioids. In this review, we highlight the mechanisms of pain in SCD and describe mechanism-based integrative approaches for treating pain.     

Pain drawings and sickle cell disease pain

This study examined the relationship of pain drawings to somatization in patients with sickle cell disease (SCD). Sixty-nine adult patients with SCD completed a pain drawing in which they shaded in areas of the body in which they experienced pain and also completed the symptom checklist (SCL) 90-R as an index of psychological distress. Analysis of variance indicated that patients who were categorized as having pain drawings with sites inconsistent with expected SCD pain patterns had somatization scores in the clinically significant range. The results suggest that health care professionals who treat SCD patients need to consider pain patterns. In individuals with pain patterns atypical for SCD, the psychological status of the patient may need to be evaluated to facilitate optimal pain management.     

Autonomically-mediated decrease in microvascular blood flow due to mental stress and pain in sickle cell disease: A target for neuromodulatory interventions

Pain and vaso-occlusive crises (VOC) are hallmark complications of sickle cell disease (SCD) and result in significant physical and psychosocial impairment. The variability in SCD pain frequency and triggers for the transition from steady state to VOC are not well understood. This paper summarizes the harmful physiological effects of pain and emotional stressors on autonomically-mediated vascular function in individuals with SCD and the effects of a cognitive, neuromodulatory intervention (i.e. hypnosis) on microvascular blood flow. We reviewed recent studies from the authors’ vascular physiology laboratory that assessed microvascular responses to laboratory stressors in individuals with SCD. Results indicate that participants with SCD exhibit marked neurally mediated vascular reactivity in response to pain, pain-related fear, and mental stress. Further, pilot study results show that engagement in hypnosis may attenuate harmful microvascular responses to pain. The collective results demonstrate that autonomically-mediated vascular responses to pain and mental stress represent an important SCD intervention target. This ongoing work provides physiological justification for the inclusion of cognitive, neuromodulatory and complementary treatments in SCD disease management and may inform the development of targeted, integrative interventions that prevent the enhancement of autonomic vascular dysfunction in SCD.     

A Biopsychosocial-Spiritual Model of Chronic Pain in Adults with Sickle Cell Disease

Chronic pain in adults with sickle cell disease (SCD) is a complex multidimensional experience that includes biologic, psychologic, sociologic, and spiritual factors. To date, three models of pain associated with SCD (i.e., biomedical model, biopsychosocial model for SCD pain, and Health Beliefs Model) have been published. The biopsychosocial multidimensional approach to chronic pain developed by Turk and Gatchel is a widely used model of chronic pain. However, this model has not been applied to chronic pain associated with SCD. In addition, a spiritual/religious dimension is not included in this model. Because spirituality/religion is central to persons affected by SCD, that dimension needs to be added to any model of chronic pain in adults with SCD. In fact, data from one study suggest that spirituality/religiosity is associated with decreased pain intensity in adults with chronic pain from SCD. A biopsychosocial-spiritual model is proposed for adults with chronic pain from SCD, because it embraces the whole person. This model includes the biologic, psychologic, sociologic, and spiritual factors relevant to adults with SCD based on past and current research. The purpose of this paper is to describe an adaptation of Turk and Gatchel’s model of chronic pain for adults with SCD and to summarize research findings that support each component of the revised model (i.e., biologic, psychologic, sociologic, spiritual). The paper concludes with a discussion of implications for the use of this model in research.     

Sensitivities to Thermal and Mechanical Stimuli: Adults With Sickle Cell Disease Compared to Healthy,Pain-Free African American Controls

Evidence supports^, but is inconclusive that sensitization contributes to chronic pain in some adults with sickle cell disease (SCD). We determined the prevalence of pain sensitization among adults with SCD pain compared with pain-free healthy adults. In a cross sectional, single session study of 186 African American outpatients with SCD pain (age 18–74 years, 59% female) and 124 healthy age, gender, and race matched control subjects (age 18–69 years, 49% female), we compared responses to standard thermal (Medoc TSA II) and mechanical stimuli (von Frey filaments). Although we observed no significant differences in thermal thresholds between controls and patients, patients with SCD had lower pain thresholds to mechanical stimuli and reported higher pain intensity scores to all thermal and mechanical stimuli at a non-painful body site. Compared with controls, about twice as many patients with SCD showed sensitization: 12% versus 23% at the anterior forearm site (P = .02), and 16% versus 32% across 3 tested sites (P = .004). Among patients with SCD, 18% exhibited some element of central sensitization. Findings indicate that persistent allodynia and hyperalgesia can be part of the SCD pain experience and should be considered when selecting therapies for SCD pain.PerspectiveCompared with matched healthy controls, quantitative sensory testing in adults with pain and sickle cell disease (SCD) demonstrates higher prevalence of sensitization, including central sensitization. The findings of allodynia and hyperalgesia may indicate neuropathic pain and could contribute to a paradigm shift in assessment and treatment of SCD pain.     

Dexmedetomidine as an Adjuvant to Analgesic Strategy During Vaso‐Occlusive Episodes in Adolescents with Sickle‐Cell Disease

Patients with sickle‐cell disease (SCD) can experience recurrent vaso‐occlusive episodes (VOEs), which are associated with severe pain. While opioids are the mainstay of analgesic therapy, in some patients with SCD, increasing opioid use is associated with continued and increasing pain. Dexmedetomidine, an α₂‐adrenoreceptor agonist with sedative and analgesic properties, has been increasingly used in the perioperative and intensive care settings and has been shown to reduce opioid requirement and to facilitate opioid weaning. Therefore, there might be a role for dexmedetomidine in pain management during VOEs in patients with SCD. Here, we present the hospital course of 3 patients who during the course of VOEs had severe pain unresponsive to opioids and ketamine and were treated with dexmedetomidine. Dexmedetomidine infusions that lasted for 3 to 6 days were associated with marked reduction in daily oral morphine‐equivalent intake and decreases in pain scores (numeric rating scale). There were no hemodynamic changes that required treatment with vasoactive or anticholinergic agents. These preliminary findings of possible beneficial effects of dexmedetomidine in decreasing opioid requirements support the hypothesis that dexmedetomidine may have a role as a possible analgesic adjuvant to mitigate VOE‐associated pain in patients with SCD.     

Practice Guidelines for the Assessment of Children With Sickle Cell Pain

issues and purpose . Pain is the most frequent and important problem for children with sickle cell disease (SCD), but it has been undertreated and understudied. A multidisciplinary group of healthcare providers, academics, and people with SCD and their families met to (1) examine the pain of vaso-occlusive events (VOE) in children and adults with SCD and (2) reach consensus about necessary improvements in care.
conclusions . Accurate assessment of pain is at the crux of effective care for children with VOE. This requires a trusting interactive relationship among patient, family, and healthcare team. Comprehensive pain assessment is a lifelong process in need of continued updating.
practice implications . Children with SCD seek treatment from nurses in many settings. Traditional care has been frustrating to both families and care providers. Children and adolescents with SCD pain would benefit from nursing care that considers patients' perspectives about pain and comfort as key determinants for treatment. A unified approach to pain assessment may be a significant factor in improving pain control.     

Review of clinical trials using early acute intervention with oral triptans for migraine management

Most of the data on triptan use are from clinical trials in which patients were instructed to wait until migraine headache pain was moderate/severe in intensity. In the real world, patients may hesitate to use a triptan until headache pain is moderate/severe because of the cost of these agents or limited supply allowed by their health service organisation. However, accumulating data indicate that early intervention with an oral triptan when headache pain is still mild may be the most effective acute treatment strategy. Economic analyses also support early triptan intervention in migraine attacks. Tolerability is expected to be particularly important in early intervention, as patients treating mild migraine pain may be more reluctant to risk adverse events. Thus, an agent selected for use as early intervention should have both a demonstrated efficacy in treating mild migraine headache and placebo-like tolerability. This article reviews retrospective and prospective clinical trials which investigated the use of triptans for early acute migraine therapy.     

AAPT Diagnostic Criteria for Chronic Sickle Cell Disease Pain

Pain in sickle cell disease (SCD) is associated with increased morbidity, mortality, and high health care costs. Although episodic acute pain is the hallmark of this disorder, there is an increasing awareness that chronic pain is part of the pain experience of many older adolescents and adults. A common set of criteria for classifying chronic pain associated with SCD would enhance SCD pain research efforts in epidemiology, pain mechanisms, and clinical trials of pain management interventions, and ultimately improve clinical assessment and management. As part of the collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks public-private partnership with the U.S. Food and Drug Administration and the American Pain Society, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy initiative developed the outline of an optimal diagnostic system for chronic pain conditions. Subsequently, a working group of experts in SCD pain was convened to generate core diagnostic criteria for chronic pain associated with SCD. The working group synthesized available literature to provide evidence for the dimensions of this disease-specific pain taxonomy. A single pain condition labeled chronic SCD pain was derived with 3 modifiers reflecting different clinical features. Future systematic research is needed to evaluate the feasibility, validity, and reliability of these criteria.

Effect of pain intensity and time to administration on responsiveness to almotriptan: results from AXERT 12.5 mg Time Versus Intensity Migraine Study (AIMS)

OBJECTIVE: To determine whether time-based early treatment, independent of pain intensity, is superior to a pain intensity-based treatment, where patients are asked to treat at least moderate intensity headaches, resulting in a reduction of overall migraine headache duration. BACKGROUND: Retrospective and prospective trials have reported improved outcomes when triptans were used early or to treat mild migraine headache pain. However, tolerability as well as efficacy may be 2 of several key issues that have prevented this new treatment paradigm from becoming universally accepted. METHODS: In this multicenter, open-label, cluster-randomized study, patients with IHS-defined migraine were instructed to treat 2 sequential migraine headaches with almotriptan 12.5 mg using either Early Treatment (ET, ie, treat at earliest onset of headache pain, within 1 hour) or Standard Treatment (ST, ie, treat when headache pain intensity is moderate or severe). The novel trial design uses total migraine headache pain duration as the primary endpoint. RESULTS: Results are presented for the first headache and include an ITT population of 757 ET and 693 ST patients. Median headache duration (time from onset of headache pain until no pain) was significantly shorter in ET patients compared to ST patients (3.18 vs 5.53 hours, P < .001). An analysis of the ET subgroup treating headache pain within 1 hour of onset revealed pain intensity, ie, treating mild or moderate versus severe pain, was significantly correlated with treatment outcomes defined by total headache duration, 2-hour pain free, sustained pain free, and use of rescue medication. Multivariate analyses comparing ST subgroups that treated within 1 hour versus greater than 1 hour after headache onset, demonstrate that both pain intensity, ie, treating moderate versus severe headache pain, and treating early versus late, were significantly correlated with total headache duration, 2-hour pain free, sustained pain free, and use of rescue medication. The overall incidence of adverse events was low; nausea and dizziness were the only adverse events with an incidence > or =1% in either treatment group (nausea: 2.5% and 1.7% and dizziness 1.1% and 0.7%, in the ET and ST groups, respectively). CONCLUSION: Total headache duration was significantly shorter in the early treatment group compared to the standard treatment group. Considering time to treatment within a relatively early range of 1 hour or less, efficacy results when treating mild versus moderate pain were similar and both were associated with better outcomes than treatment of severe pain. When considering the prognostic variables of time to treatment and headache pain intensity (limited to moderate vs severe), both were independent predictors, with time to treatment a better predictor of headache duration and rescue medication use, and pain intensity a better predictor of 2-hour pain free and sustained pain free.     

Evaluation of sex disparities in opioid use among ED patients with sickle cell disease, 2006–2015

BackgroundAcute pain from a vaso-occlusive crisis (VOC) is a leading reason patients with sickle cell disease (SCD) visit the emergency department (ED). Prior studies suggest that women and men receive disparate ED treatment for acute pain in EDs. We aim to determine sex differences in analgesic use among patients with SCD presenting to the ED.MethodsThis cross-sectional study uses data from the National Hospital Ambulatory Medical Care Survey (NHAMCS), 2006–2015. We identified ED patients with a primary diagnosis of SCD. Among patients with SCD, we evaluated sex differences in the use of opioid analgesia using logistic regression (adjusting for patient and visit characteristics). Analyses accounted for survey design and weighting.ResultsWhen evaluating the effect of sex on any opioid medication use in this population, though not significant, the odds that male patients were prescribed opioids was 1.5 (95% CI 0.8–2.8) times that of female patients after adjusting for age, the reason for visit, region, insurance status, and pain score. There was no significant difference in pain scores between male patients, 8.1 (95% CI 7.55–8.68) compared to female patients, 7.4 (95% CI 6.7–8.12).ConclusionsIn this nationally representative sample of ED visits among patients with SCD, there was no conclusive evidence of sex disparities in opioid prescribing. Though there is evidence of a trend signaling that male patients with SCD were more likely than female patients to be prescribed an opioid.     

The Headache and Pain of Spontaneous Carotid Dissection

SYNOPSIS
The clinical features of the headache and neck pain in 21 cases of spontaneous carotid dissection are described. Twenty of 21 patients had head pain or headache and of the 20, 12 had neck pain as well. One patient had neck pain only. Typically, the headache involved the ipsilateral forequarter of the head and neck pain was of local origin in the region of the upper few inches (10 cm.) of the internal carotid artery. Recognition of the headache as a prodromal manifestation may lead to prevention of a stroke through the use of anticoagulation.     

Characteristics of pain managed at home in children and adolescents with sickle cell disease by using diary self-reports

Pain can begin in the first year of life for individuals with sickle cell disease (SCD) and continue in an unpredictably recurrent manner throughout their life span. Sickle vaso-occlusive pain (sickle pain) can also occur simultaneously with pain of other origins, complicating both assessment and management. Aims of this research were to describe the reliability and validity of a daily diary for data collection with children and adolescents with SCD and to describe characteristics of vaso-occlusive sickle pain episodes (VOE) and other pain reported by children and adolescents with SCD along with home pain management strategies. Thirty-nine children and adolescents (mean age, 10.9 +/- 3.6 years) completed diaries twice daily at home for up to 3 years (mean, 417.9 +/- 272.2 diary days) with excellent compliance. Sickle pain alone was reported on 8.4% of days (n = 1515 days), whereas other pain occurred on 2.7% of days (n = 490) and both sickle pain and other pain on 5.7% (n = 1041 days). Other pain only episodes were shorter and involved fewer sites than sickle pain only episodes. Sickle pain occurred in the extremities and hips, whereas most other pain occurred in the head-neck area. Analgesic medication was taken on 85% of days of sickle pain, whereas analgesics were taken on only 60% of days with other pain. The diary used in this study is a valid and reliable self-report tool. The use of home diaries will improve the understanding of sickle pain and its management and assist in identifying other pain syndromes that may require alternative management.     

AAAPT Diagnostic Criteria for Acute Sickle Cell Disease Pain

Acute pain episodes are the most common complication in patients with sickle cell disease (SCD). Classically attributed to vaso-occlusion, recent insights suggest that chronic pain may also contribute to the pathogenesis of acute pain episodes, which adds complexity to their diagnosis and management. A taxonomy, or classification system, for acute pain in patients with SCD would aid research efforts and enhance clinical care. To meet this need, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public–private partnership with the U.S. Food and Drug Administration, the American Pain Society, and the American Academy of Pain Medicine formed the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks–American Pain Society–American Academy of Pain Medicine Pain Taxonomy initiative. One of the goals of this initiative was to develop taxonomies for acute pain disorders, including SCD. To accomplish this, a working group of experts in SCD and pain was convened. Based on available literature and expert opinion, the working group used a 5-dimenional structure (diagnostic criteria, common features, modulating factors, impact/functional consequences, and putative mechanisms) to develop an acute pain taxonomy that is specific to SCD. As part of this, a set of 4 diagnostic criteria, with 2 modifiers to account for the influence of chronic pain, are proposed to define the types of acute pain observed in patients with SCD.PerspectiveThis article presents a taxonomy for acute pain in patients with SCD. This taxonomy could help to standardize definitions of acute pain in clinical studies of patients with SCD.